Evidence map›Paper›PMID 37696839›Full record

ArticleNature communications2023

Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome.

Qiuxia Li, Quanjiang Zhang, Young-Rae Kim, Ravinder Reddy Gaddam, Julia S Jacobs, Markus M Bachschmid, Tsneem Younis, Zhiyong Zhu, Leonid Zingman, Barry London and 5 more

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 14 citations in OpenAlex.

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  9. The role ofJournal of gastrointestinal oncology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Qiuxia LiDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. qiuxia-li@uiowa.edu.ORCID http://orcid.org/0000-0001-5835-0749
Quanjiang ZhangDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0003-0182-7491
Young-Rae KimDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Ravinder Reddy GaddamDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0003-1062-5082
Julia S JacobsDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Markus M BachschmidBoston University School of Medicine, Boston, MA, 02118, USA.ORCID http://orcid.org/0000-0002-0748-5528
Tsneem YounisDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Zhiyong ZhuDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Leonid ZingmanDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Barry LondonDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Adam J RauckhorstAbboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0002-4101-0075
Eric B TaylorAbboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0003-4549-6567
Andrew W NorrisFraternal Order of Eagles Diabetes Research Center (FOEDRC), University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0001-8396-9543
Ajit VikramDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.ORCID http://orcid.org/0000-0003-3724-3842
Kaikobad IraniDivision of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. Kaikobadirani@gmail.com.ORCID http://orcid.org/0000-0001-9194-7387
University of Iowa · USBoston University · US

Funding

Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Amy Leanne Ryan · 1998 to 2026
$30.5M
PROGRAM IN HEMOSTASIS AND THROMBOSIS FOR ACADEMICT32HL007344 · NHLBI · UNIVERSITY OF IOWA · PI Anil Kumar Chauhan, Steven R Lentz · 1985 to 2026
$6.5M
SUMOylation of Voltage-Gated Sodium Channels In Neuronal Hyperexcitability of Alzheimer’s DementiaR01HL115955 · NHLBI · UNIVERSITY OF IOWA · PI IRANI, KAIKOBAD J., LONDON, BARRY · 2013 to 2023
$5.4M
Regulation of Hepatic Macronutrient Metabolism by Mitochondrial Citrate TransportR01DK104998 · NIDDK · UNIVERSITY OF IOWA · PI TAYLOR, ERIC B · 2015 to 2022
$3.2M
The SIRT1-Gpd1L-NAD+ interactome in regulation of the Neuronal Sodium Channel: Implications for Cognitive Impairment of Alzheimer’s DementiaR01HL147545 · NHLBI · UNIVERSITY OF IOWA · PI BRENNER, CHARLES M, IRANI, KAIKOBAD J. · 2019 to 2022
$2.9M
Splanchno-Hormonal Mechanisms of Cystic Fibrosis Related DiabetesR01DK115791 · NIDDK · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F, NORRIS, ANDREW W · 2018 to 2021
$1.9M
SIRTUIN1-mediated inhibition of p66shc lysine acetylation as a novel treatment for diabetic vasculopathyI01BX002940 · VA · PROVIDENCE VA MEDICAL CENTER · PI IRANI, KAIKOBAD J. · 2016 to 2024
–
Myokine musclin and exercise induced cardiac conditioningI01BX004840 · VA · IOWA CITY VA MEDICAL CENTER · PI ZINGMAN, LEONID · 2020 to 2023
–
BLRD VA I01 BX002940BLRD VA I01 BX004840NHLBI NIH HHS R01 HL115955NHLBI NIH HHS R01 HL147545NHLBI NIH HHS T32 HL007344NIDDK NIH HHS P30 DK054759NIDDK NIH HHS R01 DK104998NIDDK NIH HHS R01 DK115791
6 · The paper itself

Abstract

Downregulation of endothelial Sirtuin1 (Sirt1) in insulin resistant states contributes to vascular dysfunction. Furthermore, Sirt1 deficiency in skeletal myocytes promotes insulin resistance. Here, we show that deletion of endothelial Sirt1, while impairing endothelial function, paradoxically improves skeletal muscle insulin sensitivity. Compared to wild-type mice, male mice lacking endothelial Sirt1 (E-Sirt1-KO) preferentially utilize glucose over fat, and have higher insulin sensitivity, glucose uptake, and Akt signaling in fast-twitch skeletal muscle. Enhanced insulin sensitivity of E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation. Endothelial Sirt1 deficiency, by inhibiting autophagy and activating nuclear factor-kappa B signaling, augments expression and secretion of thymosin beta-4 (Tβ4) that promotes insulin signaling in skeletal myotubes. Thus, unlike in skeletal myocytes, Sirt1 deficiency in the endothelium promotes glucose homeostasis by stimulating skeletal muscle insulin sensitivity through a blood-borne mechanism, and augmented secretion of Tβ4 by Sirt1-deficient endothelial cells boosts insulin signaling in skeletal muscle cells.

Indexed as

Insulin ResistanceSirtuin 1AnimalsEndothelial CellsEndotheliumGlucoseInsulinMaleMiceMuscle, SkeletalSecretomeGlucoseInsulinSirt1 protein, mouseSirtuin 1

Identifiers

PMID37696839
PMCPMC10495425
OpenAlexW4386596806

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.